Functional neuroanatomy of the basal ganglia

Abstract

The "basal ganglia" refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amplified with the emergence of new data. Furthermore, parallel circuits subserve the other functions of the basal ganglia engaging associative and limbic territories. Disruption of the basal ganglia network forms the basis for several movement disorders. This article provides a comprehensive account of basal ganglia functional anatomy and chemistry and the major pathophysiological changes underlying disorders of movement. We try to answer three key questions related to the basal ganglia, as follows: What are the basal ganglia? What are they made of? How do they work? Some insight on the canonical basal ganglia model is provided, together with a selection of paradoxes and some views over the horizon in the field.

Figure 1.

Basal ganglia nuclei. Parasagittal section through the monkey brain (stained with the acetylcholinesterase method) showing the localization and boundaries of all major components of the basal ganglia system.

Figure 2.

Striatal medium-sized spiny neurons (MSNs). Striatal MSNs are the most abundant neuronal phenotype in the striatum (representing up to 95% of the total number of striatal neurons). These medium-sized neurons (20 µm in diameter) are multipolar stellate cells with radially oriented dendrites. These dendrites are covered by small postsynaptic specializations called dendritic spines. Photomicrograph taken from a striatonigral-projecting MSN, retrogradely labeled following the delivery of rabies virus into the substantia nigra pars reticulata.

Figure 3.

Striatal compartments. Although the striatum appears as a rather homogeneous structure, several histochemical and immunohistochemical stains evidence the presence of two compartments named striosomes and matrix. The photomicrograph is taken from a parasagittal section through the primate striatum. The immunohistochemical detection of the calcium-binding protein calbindin reveals the presence of a number of patchy areas with weak calbindin stain (striosomes) immersed within a background showing higher calbindin stain (matrix).

Figure 4.

Lewy bodies in dopaminergic neurons from the substantia nigra pars compacta. In humans suffering from Parkinson’s disease, dopaminergic neurons accumulate intracytoplasmatic aggregates of misfolded α-synuclein. These aggregates often adopt a circular shape and form the so-called Lewy bodies, which represent the pathological hallmark of this disease. Dual immunofluorescent detection of tyrosine hydroxylase (red channel) and α-synuclein (green channel), identifying two dopaminergic neurons from a PD patient, one of them showing a typical intracytoplasmic Lewy body.

Figure 5.

Schematic summary of the original basal ganglia model. The motor circuit is composed of a corticostriatal (putaminal) projection, two major striatofugal projection systems giving rise to the direct and indirect pathways, and the efferent pallido–thalamo–cortical projections to close the motor loop. The thickness of arrows represents the functional state of a given circuit. Thicker arrows illustrate hyperactive pathways, whereas thinner arrows represent hypoactive circuits.

Figure 6.

Basal ganglia circuits. Cartoon showing the main circuits linking the basal ganglia nuclei. Besides traditional cortico-basal ganglia-thalamocortical circuits, several transverse loops have been described in the last few years, most of them with a putative modulatory role.